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Diabetic macular edema(DME) is a major cause of vision loss and has a remarkable impact on the quality of life of diabetic patients. New pharmacological approaches based on the use of intravitreal drugs, such as corticosteroids and anti-vascular endothelial growth factor, have recently been developed for the treatment of DME. Even though laser therapy has been the standard treatment for DME, the results of several clinical trials have shown the superiority of some of these new agents to laser therapy. The purpose of this review is to briefly summarize the currently available new pharmacological treatments for DME in Japan.

Purpose: To examine the relationship between the extent of subarachnoid hemorrhage and intraocular hemorrhages in patients with subarachnoid hemorrhage., Subjects and Method: A total, of 63 patients (25 men and 38 women, mean age 58 years). The subarachnoid hemorrhage quantity was graded according to the Fisher scale and compared with hemorrhages in the ocular fundus., Results: Either vitreous or preretinal hemorrhages in either one or both eyes (vitreous hemorrhages) were present in 16 patients (25%). Retinal hemorrhages in either one or both eyes (retinal hemorrhages) were present in 12 patients (19%). Intraocular hemorrhage was absent in the other 35 patients (56%). The incidence of vitreous hemorrhage tended to be higher than the incidence of retinal hemorrhage or of the absence of hemorrhage as the rate of subarachnoid hemorrhage increased (Kruskal-Wallis, p < 0.05). There was no significant correlation between retinal hemorrhages and the absence of hemorrhage in the Fisher grade IV chi2, p > 0.05)., Conclusion: The onset of vitreous hemorrhage appears to be related to the extent of subarachnoid hemorrhage but the onset of retinal hemorrhage is not.

Background: Compare to either the middle or the long cones, short cones (S-cone) are easily damaged., Case: A 62 year-old men complained of acute tritan OS. The corrected visual acuity was 1.2 OU. Routine ocular examinations showed no remarkable abnormalities, but we detected impaired responses using S-cone ERG and blue-on-yellow perimetry OS. We diagnosed this case as acute damage of the blue cone., Conclusion: S-cone damage can be determined by electro-physiological and psychophysical examinations in cases of unilateral color abnormality.

Purpose: To report the ocular features of a father and son with central areolar choroidal dystrophy (CACD) who had similar fundus appearance., Case: Case 1. A 37-year-old man noticed impairment of his vision since several months prior to his visit to our hospital. His corrected visual acuity was 0.6 OD and 1.0 OS. Well demarcated chorioretinal atrophy with a width of 2-3 disc diameters in the macular area was observed in both ocular fundi. Optical coherence tomography (OCT) at the chorioretinal atrophy areas showed thinning of retinal thickness with a disappearance of a line corresponding to the outer segment of the photoreceptor cells, but thickening of a line of the retinal pigment epithelium. Electroretinogram(ERG) and electrooculogram(EOG) showed deteriorated responses. Case 2 was a 67-year-old man, the father of patient 1. His corrected visual acuity was 0.1 OD and 0.2 p OS. Fundus appearance was similar to that of case 1. His ERG and EOG also showed similar impaired responses. His OCT also showed findings similar to those of case 1, but the retina was thinner than in case 1 in the chorioretinal atrophy area., Discussion: The rest of the retina outside the chorioretinal atrophy area in these CACD patients also seemed to be damaged because both the ERG and EOG showed damage. These two cases revealed that a CACD patient could maintain relatively good visual acuity, even though the chorioretinal atrophy had involved the foveal area, and also indications were that retinal functions had been damaged.

Purpose: To investigate transient increased retinal hemorrhage during anticoagulant therapy and changes in the retinal venous blood flow in the course of non-ischemic central retinal vein occlusion (CRVO)., Methods: Seventeen patients(eighteen eyes) with non-ischemic CRVO were studied. The retinal vein diameter, blood velocity, and blood flow were determined by the laser Doppler method in seven patients., Results: The retinal hemorrhage increased in nine eyes (50%); however, the retinal hemorrhage was transient and it finally decreased without vision loss in seven of the eyes. The retinal hemorrhage increased in the other two eyes and they became ischemic. The vessel diameter decreased and both velocity and blood flow increased in six of the seven patients two weeks after the treatment. There was no significant change in blood flow in cases which showed a transient increase in retinal hemorrhage, and they did not show a decrease in vision; however, only one eye which became ischemic showed a decrease in blood flow., Conclusion: We can judge whether an increase in retinal hemorrhage is transient or the clinical condition is getting worse in an early stage by measuring the retinal vein blood flow quantitatively by laser Doppler flowmetry.

Purpose: To report three cases of nasopharyngeal carcinoma, exhibiting abducens nerve palsy and Horner syndrome during the medical treatment of the tumor, whose invasive cavernous sinus lesions could be detected., Subjects: The patients were two men and one woman who were referred to our department with complaints of diplopia during the clinical course of nasopharyngeal carcinoma., Results: Right abducens nerve palsy, Horner syndrome, and impairment of the 1st division of the trigeminal nerve were recognized in all patients. Magnetic resonance imaging (MRI) revealed invasive lesions in the right cavernous sinus in all three patients, with iso-intensity on T1-weighted images, which were enhanced by gadolinium., Conclusions: The abducens and sympathetic nerves run closely together in the cavernous sinus. Nasopharyngeal carcinoma is apt to invade the cavernous sinus and often impairs the abducens nerve. Therefore the presence of Horner syndrome and trigeminal palsy in combination with abducens nerve palsy should be cautiously investigated to confirm the existence of the cavernous sinus lesions.

Background: We report a case of normal-tension glaucoma(NTG) with impaired eye movements in a young patient., Case: A 22-year-old man with enlarged optic disc cuppings and visual field defects was suspected to have NTG, and was found, upon examination, to have impaired eye movements. Intraocular pressure recordings, including diurnal variation, were under 21 mmHg. Gonioscopic findings were normal. Magnetic resonance image(MRI) showed no particular findings. The patient was diagnosed with NTG. Using the 123I-iodoamphetamine single photon emission computed tomography (123I-IMP SPECT), decreased cerebral blood flow was detected in the patient's occipital lobe and an electro-oculogram showed impaired eye movements during smooth pursuit. The patient's visual field defects have increased over the last two years, but, no accompanying change in his eye movements has been observed., Conclusion: The patient in this case has NTG with impaired eye movements and decreased cerebral blood flow suggesting that some disorder of the central nervous system may be one of the causative mechanisms of NTG.

Background: Recently neonatal mortality of ELBW infants has improved remarkably, but the difficulty in preventing severe retinopathy of prematurity(ROP) or blindness implies that fundamental causes are still not resolved., Case: We encountered a case of ROP with a very good natural course in a very low birth weight(398 g) infant., Conclusion: This case suggests the possibility of predicting the course of ROP in extremely low birth weight(ELBW) infants weighing less than 500 g, and of improving their management.

It is important to study the pathogenesis in vitreoretinal diseases to develop new medical therapy. We investigated the molecular mechanisms underlying the genesis of idiopathic macular hole, exudative age-related macular degeneration (AMD), and diabetic retinopathy. We observed high levels of chymase and tryptase activity in the vitreous humor of patients with idiopathic macular hole. This activity was significantly higher than in other vitreoretinal diseases. Immunohistochemical study using monkey eyes showed the possibility that Müller cells in foveal lesions have properties similar to retinal stem cells. Intravitreal injection of chymase induced apoptosis of foveal retinal cells and fibrous change of vitreoretinal interface in the macular area. Biochemical study using cultured human Müller cells revealed that chymase caused the inhibition of growth and the induction of apoptosis in dedifferentiated Müller cells treated with basic fibroblast growth factor (bFGF). These findings show that increased production of chymase and tryptase in mast cells could be related to the pathogenesis of idiopathic macular hole. Oxidative stress and arterosclerosis may be the major causes of exudative AMD. Paraoxonase (PON) is a polymorphic protein known to prevent oxidation of low-density lipoprotein (LDL). We analyzed PON genotypes and found that two types of polymorphism were significantly different between patients with AMD and control subjects. We also investigated serum oxidized low-density lipoprotein(oxLDL) levels, PON activity, and extracellular superoxide dismutase(EC-SOD) levels. All these factors were significantly higher in patients with AMD than in controls. Titers of IgA and IgG antibodies against chlamydia pneumoniae in the serum of AMD patients were also significantly higher than in controls. These results indicate that genetic factors related to PON polymorphisms, vascular damage caused by increment of serum oxLDL and malfunction of EC-SOD, and chronic inflammation provoked by clamydia pneumoniae infection may be involved in the pathogenesis of AMD. Excess accumulation of advanced glycation end products(AGEs) has a causative role in the development of diabetic complications. We determined the concentrations of three AGEs (pentosidine, carboxy-methyllysine, and crossline) and two cytokines (VEGF, IL-6) using ELISA. The levels of the three AGEs and two cytokines in the vitreous of patients with proliferative diabetic retinopathy(PDR) were significantly higher than in controls. The concentrations of VEGF and IL-6 were strongly correlated with the level of these AGEs. Cultured human Müller cells expressed both VEGF and IL-6 mRNA and these expressions were augmented after the treatment of AGEs, while also acting as photosensitizers and accelerating the degradation of hyaluronic acid in vitro. AGEs may consequently play an important role in the pathogenesis of diabetic retinopathy by inducing the production of VEGF and IL-6 in retinal Müller cells and the acceleration of vitreous liquefaction.

A proteome has been defined as the protein complement expressed by the genome of an organism, tissue, or differentiated cell. Knowledge of complete genome sequences has led to considerable effort being increasingly devoted to the large-scale study of proteomes, that is, 'proteomics'. Commonly, two proteomes are compared by a substructive analysis in which differences due to drug treatment, culture conditions, genetic variations, or diseases can be observed. Two-dimensional gel electrophoresis and mass spectrometry are commonly used for this purpose. We applied this approach to the analysis of vitreous humor(VH) proteins. Fifty-two different proteins were identified on silver-stained 2D-gel patterns with VH proteins obtained from diabetic retinopathy and macular hole. Thirty-five proteins, which have not reported in plasma, were found in VH. Pigment epithelium-derived factor, which was reported to be a potent inhibitor of angiogenesis in cornea and vitreous was at a higher concentration in VH with diabetes than in that with macular hole. It is impressive that the inhibitor increases in the vitreous with proliferative angiogenesis. Unique applications in proteomics promise a bright future for molecular biology and hopefully for clinical chemistry.